The identification of substituted benzothiophene derivatives as PGE(2) subtype 4 receptor antagonists: From acid to non-acid

Lianhai Li; Marie-Claude Mathieu; Danielle Denis; Alex G Therien; Zhaoyin Wang

doi:10.1016/j.bmcl.2010.11.118

The identification of substituted benzothiophene derivatives as PGE(2) subtype 4 receptor antagonists: From acid to non-acid

Bioorg Med Chem Lett. 2011 Jan 15;21(2):734-7. doi: 10.1016/j.bmcl.2010.11.118. Epub 2010 Dec 3.

Authors

Lianhai Li¹, Marie-Claude Mathieu, Danielle Denis, Alex G Therien, Zhaoyin Wang

Affiliation

¹ Department of Medicinal Chemistry, Merck Frosst Centre for Therapeutic Research, 16711 Trans Canada Hwy., Kirkland, Québec, Canada H9H 3L1. lianhai_li@merck.com

PMID: 21208803
DOI: 10.1016/j.bmcl.2010.11.118

Abstract

We disclose herein our preliminary SAR study on the identification of substituted benzothiophene derivatives as PGE(2) subtype 4 receptor antagonists. A potent EP(4) antagonist 6a (K(i)=1.4nM with 10% HSA) was identified. Furthermore, we found that an acidic group was not essential for the EP(4) antagonizing activity in the series and neutral replacements were identified. This opens a new direction for future EP(4) antagonist design.

MeSH terms

Cell Line
Humans
Protein Binding
Receptors, Prostaglandin E, EP4 Subtype / antagonists & inhibitors*
Receptors, Prostaglandin E, EP4 Subtype / metabolism*
Structure-Activity Relationship
Thiophenes / chemical synthesis
Thiophenes / chemistry*
Thiophenes / pharmacology*

Substances

Receptors, Prostaglandin E, EP4 Subtype
Thiophenes
benzothiophene